Rates and predictors of radiographic sacroiliitis progression over 2 years in patients with axial spondyloarthritis
TL;DR: An elevated level of C-reactive protein (CRP) at baseline was a strong positive predictor of radiographic sacroiliitis progression in non-radiographic axial spondyloarthritis and AS (OR 3.65 and 5.08, respectively, p<0.05).
Abstract: Objective To assess the progression of radiographic sacroiliitis in a cohort of patients with early axial spondyloarthritis over a period of 2 years and to explore predictors of progression. Methods 210 patients with axial spondyloarthritis from the German Spondyloarthritis Inception Cohort have been selected for this analysis based on availability of radiographs at baseline and after 2 years of follow-up. Radiographs were centrally digitised and the sacroiliac joints were scored independently according to the grading system of the modified New York criteria for ankylosing spondylitis (AS) by two trained readers. The readers scored both time points simultaneously but were blinded for the time point and for all clinical data. Results 115 patients (54.8%) fulfilled the modified New York criteria for AS in their radiographic part in the opinion of both readers at baseline, while 95 patients (45.2%) were classified as non-radiographic axial spondyloarthritis. More patients with non-radiographic spondyloarthritis (10.5%) compared with AS (4.4%) showed an estimated ‘true’ progression by at least one grade according to both readers, although the difference between the two groups was statistically non-significant. The rate of progression from non-radiographic axial spondyloarthritis to AS was 11.6% over 2 years. An elevated level of C-reactive protein (CRP) at baseline was a strong positive predictor of radiographic sacroiliitis progression in non-radiographic axial spondyloarthritis and AS (OR 3.65 and 5.08, respectively, p Conclusion Progression of radiographic sacroiliitis by at least one grade after 2 years occurs only in a small percentage of patients with early axial spondyloarthritis. An elevated level of CRP was found to be a strong positive predictor of sacroiliitis progression.
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Leiden University Medical Center1, Ruhr University Bochum2, Ghent University Hospital3, Universidade Nova de Lisboa4, University of Zurich5, Sorbonne6, Paris Descartes University7, Semmelweis University8, VU University Medical Center9, University of Toronto10, University College London11, University of Leeds12, Erciyes University13, University of Lisbon14, University of Texas at Austin15, Charité16, Ghent University17, University of São Paulo18
TL;DR: The 2016 Assessment of SpondyloArthritis international Society-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA and three overarching principles and 13 recommendations deal with surgery and spinal fractures.
Abstract: To update and integrate the recommendations for ankylosing spondylitis and the recommendations for the use of tumour necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA) into one set applicable to the full spectrum of patients with axSpA. Following the latest version of the European League Against Rheumatism (EULAR) Standardised Operating Procedures, two systematic literature reviews first collected the evidence regarding all treatment options (pharmacological and non-pharmacological) that were published since 2009. After a discussion of the results in the steering group and presentation to the task force, overarching principles and recommendations were formulated, and consensus was obtained by informal voting. A total of 5 overarching principles and 13 recommendations were agreed on. The first three recommendations deal with personalised medicine including treatment target and monitoring. Recommendation 4 covers non-pharmacological management. Recommendation 5 describes the central role of non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice drug treatment. Recommendations 6-8 define the rather modest role of analgesics, and disprove glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for axSpA patents with predominant axial involvement. Recommendation 9 refers to biological DMARDs (bDMARDs) including TNFi and IL-17 inhibitors (IL-17i) for patients with high disease activity despite the use (or intolerance/contraindication) of at least two NSAIDs. In addition, they should either have an elevated C reactive protein and/or definite inflammation on MRI and/or radiographic evidence of sacroiliitis. Current practice is to start with a TNFi. Switching to another TNFi or an IL-17i is recommended in case TNFi fails (recommendation 10). Tapering, but not stopping a bDMARD, can be considered in patients in sustained remission (recommendation 11). The final two recommendations (12, 13) deal with surgery and spinal fractures. The 2016 Assessment of SpondyloArthritis international Society-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.
1,147 citations
Medical University of Vienna1, Chapel Allerton Hospital2, University of California3, University of Amsterdam4, University of Münster5, University of Washington6, University of Texas Health Science Center at Houston7, University of Rochester Medical Center8, Charité9, National Autonomous University of Mexico10, Sofia University11, Oregon Health & Science University12, Ghent University Hospital13, Pierre-and-Marie-Curie University14, Chung Shan Medical University15, Leiden University Medical Center16
TL;DR: The task force defined the treatment target for SpA as remission or, alternatively, low disease activity, being aware that the evidence base is not strong and needs to be expanded by future research.
Abstract: Background Therapeutic targets have been defined for diseases like diabetes, hypertension or rheumatoid arthritis and adhering to them has improved outcomes. Such targets are just emerging for spondyloarthritis (SpA). Objective To define the treatment target for SpA including ankylosing spondylitis and psoriatic arthritis (PsA) and develop recommendations for achieving the target, including a treat-to-target management strategy. Methods Based on results of a systematic literature review and expert opinion, a task force of expert physicians and patients developed recommendations which were broadly discussed and voted upon in a Delphi-like process. Level of evidence, grade and strength of the recommendations were derived by respective means. The commonalities between axial SpA, peripheral SpA and PsA were discussed in detail. Results Although the literature review did not reveal trials comparing a treat-to-target approach with another or no strategy, it provided indirect evidence regarding an optimised approach to therapy that facilitated the development of recommendations. The group agreed on 5 overarching principles and 11 recommendations; 9 of these recommendations related commonly to the whole spectrum of SpA and PsA, and only 2 were designed separately for axial SpA, peripheral SpA and PsA. The main treatment target, which should be based on a shared decision with the patient, was defined as remission, with the alternative target of low disease activity. Follow-up examinations at regular intervals that depend on the patient9s status should safeguard the evolution of disease activity towards the targeted goal. Additional recommendations relate to extra-articular and extramusculoskeletal aspects and other important factors, such as comorbidity. While the level of evidence was generally quite low, the mean strength of recommendation was 9–10 (10: maximum agreement) for all recommendations. A research agenda was formulated. Conclusions The task force defined the treatment target as remission or, alternatively, low disease activity, being aware that the evidence base is not strong and needs to be expanded by future research. These recommendations can inform the various stakeholders about expert opinion that aims for reaching optimal outcomes of SpA.
419 citations
TL;DR: The presence of radiographic damage at baseline (syndesmophytes), elevated levels of acute-phase reactants, and cigarette smoking were all independently associated with spinal radiographic progression in patients with early axial SpA.
Abstract: Objective
To assess prospectively the rates and to explore predictors of spinal radiographic progression over 2 years in a cohort of patients with early axial spondylarthritis (SpA).
Methods
Two hundred ten patients with axial SpA from the German Spondyloarthritis Inception Cohort were selected for this analysis based on the availability of radiographs at baseline and after 2 years of followup. Spinal radiographs were scored by 2 trained readers in a blinded, randomly selected order according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Spinal radiographic progression was defined as worsening of the mean mSASSS by ≥2 units over 2 years.
Results
Among the patients with axial SpA, 14.3% showed spinal radiographic progression after 2 years (20% of those with AS and 7.4% of those with nonradiographic axial SpA). The following parameters were independently associated with spinal radiographic progression: presence of syndesmophytes at baseline (odds ratio [OR] 6.29, P < 0.001), elevated levels of markers of systemic inflammation (for the erythrocyte sedimentation rate, OR 4.04, P = 0.001; for C-reactive protein level time-averaged over 2 years, OR 3.81, P = 0.001), and cigarette smoking (OR 2.75, P = 0.012). These associations were confirmed by multivariate logistic regression analysis. No clear association with spinal radiographic progression was observed for HLA–B27 status, sex, age, disease duration, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, presence of peripheral arthritis, enthesitis, psoriasis, treatment with nonsteroidal antiinflammatory drugs, or treatment with disease-modifying antirheumatic drugs at baseline.
Conclusion
The presence of radiographic damage at baseline (syndesmophytes), elevated levels of acute-phase reactants, and cigarette smoking were all independently associated with spinal radiographic progression in patients with early axial SpA.
394 citations
TL;DR: A high NSAIDs intake over 2 years is associated with retarded radiographic spinal progression in AS, and in non-radiographic axial SpA this effect is less evident, probably due to a low grade of new bone formation in the spine at this stage.
Abstract: Objective To investigate the influence of non-steroidal anti-inflammatory drugs (NSAIDs) intake on radiographic spinal progression over 2 years in patients with ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (SpA). Methods 164 patients with axial SpA (88 with AS and 76 with non-radiographic axial SpA) were selected for this analysis based on availability of spinal radiographs at baseline and after 2 years of follow-up and the data on NSAIDs intake. Spinal radiographs were scored by two trained readers in a concealed randomly selected order according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) system. An index of the NSAID intake counting both dose and duration of drug intake was calculated. Results High NSAIDs intake (NSAID index≥50) in AS was associated with lower likelihood of significant radiographic progression defined as an mSASSS worsening by ≥2 units: OR=0.15, 95% CI 0.02 to 0.96, p=0.045 (adjusted for baseline structural damage, elevated C reactive protein (CRP) and smoking status) in comparison with patients with low NSAIDs intake (NSAID index Conclusion A high NSAIDs intake over 2 years is associated with retarded radiographic spinal progression in AS. In non-radiographic axial SpA this effect is less evident, probably due to a low grade of new bone formation in the spine at this stage.
291 citations
TL;DR: Patients with axial spondylarthritis who have structural changes in the sacroiliac joints and/or the spine have been classified as having ankylosing spondYLitis (AS), while those without such changes are nowclassified as having nonradiographic axial SpA (nr‐axSpA).
Abstract: Objective Patients with axial spondylarthritis (SpA) who have structural changes in the sacroiliac joints and/or the spine have been classified as having ankylosing spondylitis (AS), while those without such changes are now classified as having nonradiographic axial SpA (nr-axSpA). The differentiating features are incompletely understood. Methods Data from 100 consecutive patients with axial SpA not treated with tumor necrosis factor antagonists were compared clinically and with laboratory parameters, spinal radiographs, and magnetic resonance imaging (MRI) of the spine. Standardized clinical assessment tools were used to assess health status. Results AS was diagnosed in 56 patients and nr-axSpA in 44 patients. Signs of inflammation were significantly higher in patients with AS than in patients with nr-axSpA, with a median C-reactive protein level of 8.0 versus 3.8 mg/liter, a median Ankylosing Spondylitis Disease Activity Score of 2.2 versus 2.8, respectively, and a median amount of spinal inflammatory lesions on MRI of 2.0 versus 0.0, respectively. Significant differences between these 2 groups were seen in sex (76.8% male AS patients versus 31.8% male nr-axSpA patients). Clinical variables did not differ between patients with AS and nr-axSpA (Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Quality of Life questionnaire, Short Form 36 health survey). Conclusion Patients with nr-axSpA were characterized by the low proportion of male patients and the low burden of inflammation compared to patients with AS. While both groups did not differ regarding health status, disease activity, and physical function, they did differ in signs of inflammation; all were higher in patients with AS. Since many patients with nr-axSpA had not developed structural changes after years of symptoms, we propose that those patients should not be regarded as having preradiographic AS but rather as having nr-axSpA.
284 citations
Cites background or methods from "Rates and predictors of radiographi..."
...The data from the GESPIC cohort have suggested that the proportion of patients fulfilling the New York criteria within 2 years was 10% (22)....
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...For example, in the GESPIC, male sex and CRP levels were associated with structural radiographic changes (22)....
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References
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TL;DR: The study showed the clinical history screening test for AS to be moderately sensitive, but it might be better in clinical practice, and substitution of the Rome pain criterion for the New York pain criterion is proposed.
Abstract: The New York and the Rome diagnostic criteria for ankylosing spondylitis (AS) and the clinical history screening test for AS were evaluated in relatives of AS patients and in population control subjects. The New York criterion of pain in the (dorso) lumbar spine lacks specificity, and the chest expansion criterion is too insensitive. The Rome criterion of low back pain for more than 3 months is very useful. Our study showed the clinical history screening test for AS to be moderately sensitive, but it might be better in clinical practice. As a modification of the New York criteria, substitution of the Rome pain criterion for the New York pain criterion is proposed.
5,143 citations
Charité1, Leiden University2, Maastricht University3, Dokuz Eylül University4, Ruhr University Bochum5, University of Córdoba (Spain)6, University of Paris7, Sun Yat-sen University8, Ege University9, University of Alberta10, Ghent University11, University of Copenhagen12, Fırat University13, Barking, Havering and Redbridge University Hospitals NHS Trust14, Chung Shan Medical University15
TL;DR: The new ASAS classification criteria for axial SpA can reliably classify patients for clinical studies and may help rheumatologists in clinical practice in diagnosing axial spondyloarthritis in those with chronic back pain.
Abstract: Objective: To validate and refine two sets of candidate criteria for the classification/diagnosis of axial spondyloarthritis (SpA). Methods: All Assessment of SpondyloArthritis international Society (ASAS) members were invited to include consecutively new patients with chronic (⩾3 months) back pain of unknown origin that began before 45 years of age. The candidate criteria were first tested in the entire cohort of 649 patients from 25 centres, and then refined in a random selection of 40% of cases and thereafter validated in the remaining 60%. Results: Upon diagnostic work-up, axial SpA was diagnosed in 60.2% of the cohort. Of these, 70% did not fulfil modified New York criteria and, therefore, were classified as having “non-radiographic” axial SpA. Refinement of the candidate criteria resulted in new ASAS classification criteria that are defined as: the presence of sacroiliitis by radiography or by magnetic resonance imaging (MRI) plus at least one SpA feature (“imaging arm”) or the presence of HLA-B27 plus at least two SpA features (“clinical arm”). The sensitivity and specificity of the entire set of the new criteria were 82.9% and 84.4%, and for the imaging arm alone 66.2% and 97.3%, respectively. The specificity of the new criteria was much better than that of the European Spondylarthropathy Study Group criteria modified for MRI (sensitivity 85.1%, specificity 65.1%) and slightly better than that of the modified Amor criteria (sensitivity 82.9, specificity 77.5%). Conclusion: The new ASAS classification criteria for axial SpA can reliably classify patients for clinical studies and may help rheumatologists in clinical practice in diagnosing axial SpA in those with chronic back pain. Trial registration number: NCT00328068.
2,704 citations
TL;DR: The proposed classification criteria for spondylarthropathy are easy to apply in clinical practice and performed well in all 7 participating centers and are regarded as preliminary until they have been further evaluated in other settings.
Abstract: Classification criteria for most of the disorders belonging to the spondylarthropathy group already exist. However, the spectrum of spondylarthropathy is wider than the sum of these disorders suggests. Seronegative oligoarthritis, dactylitis or polyarthritis of the lower extremities, heel pain due to enthesitis, and other undifferentiated cases of spondylarthropathy have been ignored in epidemiologic studies because of the inadequacy of existing criteria. In order to define classification criteria that also encompass patients with undifferentiated spondylarthropathy, we studied 403 patients with all forms of spondylarthropathy and 674 control patients with other rheumatic diseases. The diagnoses were based on the local clinical expert's opinion. The 403 patients included 168 with ankylosing spondylitis, 68 with psoriatic arthritis, 41 with reactive arthritis, 17 with inflammatory bowel disease and arthritis, and 109 with unclassified spondylarthropathy. Based on statistical analysis and clinical reasoning, we propose the following classification criteria for spondylarthropathy: inflammatory spinal pain or synovitis (asymmetric or predominantly in the lower limbs), together with at least 1 of the following: positive family history, psoriasis, inflammatory bowel disease, urethritis, or acute diarrhea, alternating buttock pain, enthesopathy, or sacroiliitis as determined from radiography of the pelvic region. These criteria resulted in a sensitivity of 87% and a specificity of 87%. The proposed classification criteria are easy to apply in clinical practice and performed well in all 7 participating centers. However, we regard them as preliminary until they have been further evaluated in other settings.
2,164 citations
TL;DR: The results show that treatment with infliximab is effective in patients with active ankylosing spondylitis, and since there are some potentially serious adverse effects, it is recommended that this treatment mainly be used in co-operation with rheumatological centres.
1,227 citations
Charité1, Maastricht University2, Leiden University3, Ruhr University Bochum4, National Autonomous University of Mexico5, University of Córdoba (Spain)6, University of California, San Francisco7, VU University Amsterdam8, University of Paris9, University of Leeds10, University of Toronto11, University of Helsinki12, University of Alberta13, Ghent University14, Glasgow Royal Infirmary15, Katholieke Universiteit Leuven16
TL;DR: The ASAS group has developed candidate criteria for the classification of axial SpA that include patients without radiographic sacroiliitis, and the candidate criteria need to be validated in an independent international study.
Abstract: Objective: Non-radiographic axial spondyloarthritis (SpA) is characterised by a lack of definitive radiographic sacroiliitis and is considered an early stage of ankylosing spondylitis. The objective of this study was to develop candidate classification criteria for axial SpA that include patients with but also without radiographic sacroiliitis. Methods: Seventy-one patients with possible axial SpA, most of whom were lacking definite radiographic sacroiliitis, were reviewed as “paper patients” by 20 experts from the Assessment of SpondyloArthritis international Society (ASAS). Unequivocally classifiable patients were identified based on the aggregate expert opinion in conjunction with the expert-reported level of certainty of their judgement. Draft criteria for axial SpA were formulated and tested using classifiable patients. Results: Active sacroiliitis on magnetic resonance imaging (MRI) (odds ratio 45, 95% CI 5.3 to 383; p x rays in conjunction with one SpA feature or, if sacroilitiis is absent, in the presence of at least three SpA features. In a second set of candidate criteria, inflammatory back pain is obligatory in the clinical arm (sensitivity 86.1%; specificity 94.7%). Conclusion: The ASAS group has developed candidate criteria for the classification of axial SpA that include patients without radiographic sacroiliitis. The candidate criteria need to be validated in an independent international study.
778 citations